Virtual Screening, Molecular Docking and Molecular Dynamics Studies For Discovery of Novel Vegfr-2 Inhibitors

VEGFR-2 is considered as potential target for cancer therapy. In this work, the stability, binding mode between the VEGFR-2 protein and its ligand have been evaluated using the pharmacophore guided virtual screening (VS), molecular docking, and molecular dynamics (MD) simulations. The small molecule VEGFR-2 inhibitors were identified through virtual screening of chemical databases based on pharmacophore guided VS approach, that searches multi-conformer representations efficiently using PHASE module of Schrodinger. In addition, the molecular docking, using GLIDE module of Schrodinger; and molecular dynamics simulation, using GROMACS software were performed to study the interaction between the protein and the ligand. Molecular docking enables the extraordinary structural diversity of synthetic products to be harnessed in an efficient manner. The best six ligands (ZINC01056202, ZINC06091460, ZINC06091450, ZINC04107510, ZINC04623218, and ZINC81582433) with different scaffolds are selected from docking studies. VEGFR-2 and ligand complex was found to be stable at room temperature demonstrated by 1000 ps molecular dynamic simulation study using water as a solvent. The predicted inhibitors are quite novel compared with the known VEGFR-2 inhibitors. The work provides insight for molecular understanding of VEGFR-2 and can be used for development of anticancer drugs.